Urinary tract infection (UTI) is the most common urological disease in the United States and the second most common bacterial infection of any organ system, UTIs are a major cause of patient morbidity and health-care expenditure for all age groups. UTIs account for approximately 7 million office visits, more than 1 million visits to emergency departments, and approximately 100,000 hospitalizations each year. The estimated annual cost to the United States health-care system is approximately $1.6 billion. In patients who are at risk for complicated UTIs (e.g. obstructive uropathy, immunocompromised state, neurogenic bladder, congenital urinary tract anomalies, and indwelling foreign bodies), delay in diagnosis and initiation of appropriate medical intervention can lead to life threatening systemic infections or permanently reduced renal function.
The traditional basis for the identification of urinary pathogens (uropathogens) is urine culture. The major drawback of the urine culture is the time lapse of approximately 1-2 days between specimen collection and pathogen identification. In the absence of expeditious laboratory diagnosis, clinicians frequently need to decide whether to initiate empiric outpatient or inpatient antimicrobial treatment without supportive laboratory evidence. Injudicious use of antimicrobial agents contributes to the incidence of adverse drug reactions and the emergence of antibiotic resistant pathogens. Urine specimens are the most common type of body fluid submitted for culture to clinical microbiology laboratories. Significant resources at these clinical laboratories are devoted to the time-consuming processing of urine specimens, although the majority of these specimens are negative or yield insignificant quantities of bacteria. A rapid test that could identify the uropathogens, or confirm the presence or absence of clinically significant bacteria with high sensitivity and specificity, would significantly reduce the workload of clinical microbiology laboratories. In addition a test that determined the susceptibility of a given specimen to antibiotic treatment would avoid the health risks associated with administering antibiotics to a patient with an antibiotic-resistant infection.
Molecular biological techniques based on DNA hybridization are increasingly utilized in clinical diagnostic testing, and are especially useful in the identification of infectious agents that cannot be cultured. Hybridization of oligonucleotides to the unique molecular sequence of an organism's DNA or RNA is highly sensitive for pathogen-specific identification, surpassing culturing methods that depend on morphological and biochemical characteristics. More rapid realtime polymerase chain reaction (PCR) quantification involving amplification of target DNA or RNA currently requires technically demanding specimen processing procedures. Despite the inherent advantages of molecular diagnostic approaches, this issue has thus far precluded widespread application of molecular techniques in clinical diagnostics.
Recent advances in sensors and actuators based on microfabrication and bionanotechnology have led to an intense interest in their development for biomedical applications. Microscale devices are particularly compatible to detect and manipulate biological molecules of interest, such as nucleic acids and proteins, with nanoscale precision. As an example of micro-devices well-suited for clinical diagnostic testing, electrochemical sensors offer sensitivity, selectivity, portability and relative low cost for nucleic acids detection. The basic electrochemical sensor design is comprised of a nucleic acid layer coupled with electrochemical transducers to detect sequence-specific hybridization events.
There remains a need for improved tools to permit the rapid detection of pathogens, and to permit assessment of the susceptibility of bacterial pathogens to antimicrobial treatment. In particular, there is a need for probes capable of detecting and distinguishing the various bacterial pathogens, as well as more rapid methods to obtain assay results needed to guide effective treatment.